U.S. patent number 7,057,722 [Application Number 10/406,737] was granted by the patent office on 2006-06-06 for method and apparatus for determining the homogeneity of a granulation during tableting.
This patent grant is currently assigned to Euro-Celtique S.A.. Invention is credited to Kevin C. Bynum, Emil Ciurczak, Lane Gehrlein, Gary Ritchie.
United States Patent |
7,057,722 |
Gehrlein , et al. |
June 6, 2006 |
Method and apparatus for determining the homogeneity of a
granulation during tableting
Abstract
An apparatus for detecting the homogeneity of a pharmaceutical
mixture has a hopper for containing a mixture of two or more
pharmaceutical components and that is situated within a production
line of preparation of a pharmaceutical dosage form. A spectroscope
is mounted to the hopper for measuring spectroscopic
characteristics of the mixture, and a processing device that is not
physically coupled to the spectroscope analyzes the spectroscopic
characteristics of the mixture and derives information regarding
the homogeneity of the mixture. The spectroscope wirelessly sends
the spectroscopic characteristics to the processing device, which
derives information regarding the homogeneity of the mixture. The
wireless transmission of the spectroscopic characteristics can be
done through infrared radiation or near infrared radiation, and the
spectroscopic characteristics can be converted to digital signals
prior to being transmitted.
Inventors: |
Gehrlein; Lane (Pine Island,
NY), Ciurczak; Emil (Goldens Bridge, NY), Ritchie;
Gary (Kent, CT), Bynum; Kevin C. (Yonkers, NY) |
Assignee: |
Euro-Celtique S.A. (Luxembourg,
LU)
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Family
ID: |
29250469 |
Appl.
No.: |
10/406,737 |
Filed: |
April 3, 2003 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20040012781 A1 |
Jan 22, 2004 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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60369823 |
Apr 4, 2002 |
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Current U.S.
Class: |
356/328; 366/143;
366/142; 356/419 |
Current CPC
Class: |
G01N
21/3563 (20130101); G01N 21/85 (20130101); B30B
15/304 (20130101); B30B 11/08 (20130101); G01N
2021/0118 (20130101); G01N 2021/8592 (20130101) |
Current International
Class: |
G01J
3/28 (20060101); B01F 9/00 (20060101) |
Field of
Search: |
;356/326,328,72,419
;366/142,143 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0160503 |
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Aug 2001 |
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WO |
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WO 02/18912 |
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Mar 2002 |
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WO |
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Primary Examiner: Evans; F. L.
Attorney, Agent or Firm: Davidson, Davidson & Kappel,
LLC
Parent Case Text
This application claims priority from U.S. Provisional Application
No. 60/369,823 filed on Apr. 4, 2002, the entire disclosure of
which is hereby incorporated by reference.
Claims
What is claimed is:
1. An apparatus for detecting a spectroscopic characteristic of a
pharmaceutical mixture, the apparatus comprising: a hopper for
containing a mixture of two or more pharmaceutical components; a
spectrometer mounted to said hopper, the spectrometer measuring a
spectroscopic characteristic of the contents of said hopper, the
spectrometer having associated therewith a transmitter, the
transmitter operable to wirelessly transmit information indicative
of the spectroscopic characteristic; and a processing device not
physically coupled to said spectrometer and not physically coupled
to said transmitter, said processing device wirelessly receiving
the information from the transmitter and being operable to
determine a moisture content of the mixture from the
information.
2. The apparatus of claim 1, wherein said processing device is
remote from said spectrometer.
3. The apparatus of claim 1, wherein said processing device is
remote from said transmitter.
4. The apparatus of claim 1, wherein the processing device is
operable to determine a homogeneity of the mixture from the
information.
5. The apparatus according to claim 1, wherein the apparatus
includes a plurality of spectrometers mounted to said hopper, each
spectrometer having associated therewith a transmitter operable to
wirelessly transmit information indicative of the spectroscopic
characteristic, and wherein the processing device wirelessly
receives information from each of the transmitters.
6. The apparatus according to claim 5, wherein the hopper includes
an input for receiving the mixture, and output for dispensing the
mixture, and wherein the mixture follows a transmission path
between the input and the output, and wherein the spectrometers are
spaced apart along the transmission path.
7. The apparatus according to claim 5, wherein the hopper includes
an input for receiving the mixture, and output for dispensing the
mixture, and wherein the mixture follows a transmission path
between the input and the output, and wherein the spectrometers are
spaced apart along a plane perpendicular to the transmission
path.
8. An apparatus for detecting the homogeneity of a pharmaceutical
mixture, the apparatus comprising: a hopper for containing a
mixture of two or more pharmaceutical components, said hopper being
situated within a production line of preparation of a
pharmaceutical dosage form from said mixture; a spectrometer
mounted to said hopper, said spectrometer comprising a light source
including a fiber optic bundle for irradiating said contents of
said hopper and illuminating a plurality of positions in a neck
region of said hopper and further comprising at least one detector
for detecting radiation reflected off or transmitted through said
mixture, the spectrometer measuring spectroscopic characteristics
of the contents of said hopper; a processing device not physically
coupled to said spectrometer, said processing device being adapted
to analyze information regarding said spectroscopic characteristics
of said hopper contents and derive therefrom information regarding
the homogeneity of said mixture of pharmaceutical components; a
plurality of optical fibers spaced apart on the neck for receiving
radiation reflected off or transmitted through said mixture and
delivering said respective radiation to said at least one detector;
and a switching device coupled to each of the plurality of optical
fibers and to the at least one detector, the switching device
configured to connect one of said respective optical fiber at a
time to said at least one detector; wherein said spectrometer
measures spectroscopic characteristics of the contents of said
hopper and wirelessly sends information regarding said
spectroscopic characteristics to said processing device, and said
processing device derives, from said spectroscopic information,
information regarding the homogeneity of said mixture of
pharmaceutical components.
9. The apparatus of claim 8, wherein said processing device is
remote from said spectrometer.
10. The apparatus of claim 8, wherein said device for measuring
spectroscopic characteristics comprises a transmitter coupled
thereto for wirelessly sending said information regarding said
spectroscopic characteristics, and wherein said processing device
is remote from said transmitter.
11. The apparatus of claim 8, wherein said device for measuring
spectroscopic characteristics comprises a transmitter coupled
thereto for wirelessly sending said information regarding said
spectroscopic characteristics, and wherein said processing device
comprises a receiver coupled thereto for wirelessly receiving said
information regarding said spectroscopic characteristics.
12. The apparatus of claim 11, wherein said information regarding
said spectroscopic characteristics is converted to digital signals
prior to being wirelessly sent to said processing device.
13. The apparatus of claim 11, further comprising a display device
coupled to said processing device for display of said information
regarding the homogeneity of said mixture of pharmaceutical
components.
14. The apparatus of claim 8, wherein said hopper comprises an
aperture, and wherein said measuring device is mounted to said
hopper adjacent said aperture.
15. The apparatus of claim 8, wherein at least one of said
plurality of optical fibers associated with said at least one
detector is on a side of said hopper proximate to at least one of
said optic fibers associated with said light source for detecting
light reflected off said mixture.
16. The apparatus of claim 8, wherein at least one of said
plurality of optical fibers associated with said at least one
detector is on a side of said hopper remote from at least one of
said optic fibers associated with said light source for detecting
light transmitted through said mixture.
17. The apparatus of claim 8, wherein said light source emits
radiation in multiple wavelengths, said apparatus further
comprising a filter for restricting passage of light through said
filter in only a specific predetermined range of wavelengths.
18. The apparatus of claim 17, wherein said filter is situated
between said light source and said mixture, such that said filter
allows passage of light in only a specific predetermined range of
wavelengths to pass to said mixture.
19. The apparatus of claim 17, wherein said filter is situated
between said mixture and said at least one detector, such that said
filter allows passage of only a specific predetermined range of
wavelengths reflected off or transmitted through said mixture to
pass to said at least one detector.
20. The apparatus of claim 17, wherein said filter is at least one
linear variable filter.
21. The apparatus of claim 20, further comprising a solid state
translation device operatively connected to said at least one
linear variable filter and configured for moving said at least one
linear variable filter.
22. The apparatus of claim 21, wherein said at least one detector
comprises a plurality of detectors.
23. The apparatus of claim 21, wherein said solid state translation
device is a piezoelectric bimorph.
24. The apparatus of claim 23, further comprising a lever device
coupling said piezoelectric bimorph to said at least one linear
variable filter and configured for amplifying a movement of said at
least one linear variable filter relative to a movement of said
piezoelectric bimorph.
25. The apparatus of claim 20, wherein said detector is at least
one array detector.
26. The apparatus of claim 20, wherein said detector is at least
one diode.
27. The apparatus of claim 17, wherein the filter is a bandpass
filter.
28. The apparatus of claim 27, wherein the filter includes a
plurality of bandpass filters.
29. The apparatus of claim 17, wherein said filter is a
grating.
30. The apparatus of claim 29, wherein said grating is a
diffraction grating.
31. The apparatus of claim 8, wherein said light source emits light
in only a specific predetermined range of wavelengths, and wherein
said at least one detector detects light reflected off or
transmitted through said mixture in said specific predetermined
range of wavelengths.
32. The apparatus of claim 8, wherein said light source emits light
in multiple wavelengths, and wherein each of said at least one
detector detects light reflected off or transmitted through said
mixture in only a specific predetermined range of wavelengths.
33. The apparatus of claim 8, wherein said measuring device sends
information regarding said spectroscopic characteristics to said
processing device through infrared radiation or near infrared
radiation.
34. An apparatus for determining spectroscopic characteristics of
one or more components, comprising: a hopper for adding one or more
components to a tableting/encapsulation machine, the hopper having
an aperture fitted with a window, one side of the window forming a
portion of an interior surface of the hopper; a light source for
transmitting a beam of light, the beam impinging the window, and
then a detector, the detector optically connected to the beam of
light and converting the beam of light into a digital signal; a
transmitter for receiving the digital signal from the detector and
sending the digital signal to a processor via a wireless link; and
a processor for analyzing a spectroscopic characteristic of the one
or more components based on the digital signal, wherein the
spectroscopic characteristic is indicative of a moisture content of
the one or more components.
35. The apparatus of claim 34, wherein said transmitter is coupled
to said processor, the transmitter receiving the profile from the
processor and transmitting the spectroscopic characteristics as a
second digital signal to a receiver via a wireless link.
36. The apparatus of claim 34, wherein the one or more components
form a mixture, and wherein the spectroscopic characteristic is
indicative of the homogeneity of the mixture.
37. A method for determining the homogeneity of a pharmaceutical
mixture in a hopper, comprising the steps of: feeding a mixture of
at least two pharmaceutical substances into a hopper, the hopper
having a window, one face of the window forming a portion of an
interior surface of the hopper and the window optically connected
to a light source; projecting light from said light source onto
said mixture; receiving information from a detector that is
optically connected to the window as the pharmaceutical mixture is
being mixed; and analyzing the information from the detector; and
determining the homogeneity and moisture content of the
pharmaceutical mixture.
38. The apparatus of claim 8, wherein the mixture is a
granulation.
39. The apparatus of claim 8, wherein the mixture is a dry
blend.
40. The method of claim 37, wherein the mixture is a
granulation.
41. The method of claim 37, wherein the mixture is a dry blend.
42. A method for detecting a spectroscopic characteristic of a
pharmaceutical mixture in a hopper, comprising the steps of:
feeding a mixture of one or more pharmaceutical components into a
hopper; measuring a spectroscopic characteristic of the contents of
said hopper with a spectrometer mounted to said hopper,
transmitting the spectroscopic characteristic to a processing
device via a transmitter, the transmitter associated with the
spectrometer and operable to wirelessly transmit information
indicative of the spectroscopic characteristic, and determining a
moisture content of the mixture from the spectroscopic
characteristic.
43. The method of claim 42 further comprising the step of
receiving, via a wireless connection, the spectroscopic
characteristic at a processing device, the processing device not
physically coupled to said spectrometer and not physically coupled
to said transmitter.
44. The method of claim 43, wherein said processing device is
remote from said spectrometer.
45. The method of claim 43, wherein said processing device is
remote from said transmitter.
46. The method of claim 43, further comprising the step of
determining a homogeneity of the mixture from the spectroscopic
characteristic.
47. The method of claim 43, wherein the spectrometer further
comprises a plurality of spectrometers; and wherein the transmitter
further comprises a plurality of transmitters each transmitter
associated with at least on one of the spectrometers; and wherein
the step of receiving further comprises receiving a plurality of
spectroscopic characteristics from each of the transmitters.
48. The method of claim 47, wherein the hopper includes an input
for receiving the mixture, and output for dispensing the mixture;
wherein the mixture follows a transmission path between the input
and the output; and wherein the spectrometers are spaced apart
along the transmission path.
49. The method of claim 47, wherein the hopper includes an input
for receiving the mixture, and an output for dispensing the
mixture; wherein the mixture follows a transmission path between
the input and the output; and wherein the spectrometers are spaced
apart along a plane perpendicular to the transmission path.
50. A method for detecting a spectroscopic characteristic of a
pharmaceutical mixture in a hopper, comprising the steps of:
feeding a mixture of one or more pharmaceutical components into a
hopper; measuring a spectroscopic characteristic of the contents of
said hopper with a spectrometer mounted to said hopper,
transmitting the spectroscopic characteristic to a processing
device via a transmitter, the transmitter associated with the
spectrometer and operable to wirelessly transmit information
indicative of the spectroscopic characteristic, and pre-treating
the spectroscopic characteristic with a pre-treatment technique
selected from the group consisting of: a baseline correction, a
normalization of the spectral data, a first derivative on the
spectral data, a second derivative on the spectral data, a
multiplicative scatter correction on the spectral data, a smoothing
transform on the spectral data, a Savitsky-Golay first derivative,
a Savitaky-Golay second derivative, a mean-centering, a
Kubelka-Munk transform, and a conversion from
reflectance/transmittance to absorbence.
51. A method for detecting a spectroscopic characteristic of a
pharmaceutical mixture in a hopper, comprising the steps of:
feeding a mixture of one or more pharmaceutical components into a
hopper; measuring a spectroscopic characteristic of the contents of
said hopper with a spectrometer mounted to said hopper,
transmitting the spectroscopic characteristic to a processing
device via a transmitter, the transmitter associated with the
spectrometer and operable to wirelessly transmit information
indicative of the spectroscopic characteristic. pre-treating the
spectroscopic characteristic with a pre-treatment technique, and
applying a data reduction technique to the spectroscopic
characteristic.
52. The method of claim 51, wherein the data reduction technique is
selected from the group consisting of: partial least squares, a
neural net, a classical least squares, a principal component
regression, and a multiple linear regression.
53. The method of claim 50, further comprising applying a data
reduction technique to the pre-treated spectroscopic
characteristic.
54. The method of claim 53, wherein the data reduction technique is
selected from the group consisting of a partial least squares, a
neural net, a classical least squares, a principal component
regression, and a multiple linear regression.
55. The apparatus of claim 8, farther comprising a tableting press
for tableting the mixture, the tableting press located downstream
from the hopper and coupled to an output of the hopper.
56. The apparatus of claim 8, further comprising a mixer for mixing
two or more pharmaceutical compositions, the mixer located upstream
from the hopper and coupled to an input of the hopper.
57. The apparatus of claim 8, further comprising an encapsulating
press for encapsulating mixture, the encapsulating press located
downstream from the hopper and coupled to an output of the
hopper.
58. The apparatus of claim 55, wherein the hopper is integrated
into the tableting press.
59. The apparatus of claim 56, wherein the mixer is integrated into
the hopper.
60. The apparatus of claim 57, wherein the hopper is integrated
into the encapsulating press.
61. The apparatus of claim 8, wherein said light source includes a
plurality of near-infrared light emitting diodes, each for
illuminating a respective position of the plurality of
positions.
62. An apparatus for detecting the homogeneity of a pharmaceutical
mixture, the apparatus comprising: a hopper for containing a
mixture of two or more pharmaceutical components, said hopper being
situated within a production line of preparation of a
pharmaceutical dosage form from said mixture; a spectrometer
mounted to said hopper, said spectrometer comprising a light source
including a fiber optic bundle for irradiating said contents of
said hopper and illuminating a plurality of positions in a neck
region of said hopper and further comprising at least one detector
for detecting radiation reflected off or transmitted through said
mixture, wherein said at least one detector is disposed in said
neck region for detecting light reflected off or transmitted
through said mixture, the spectrometer measuring spectroscopic
characteristics of the contents of said hopper; and a processing
device not physically coupled to said spectrometer, said processing
device being adapted to analyze information regarding said
spectroscopic characteristics of said hopper contents and derive
therefrom information regarding the homogeneity of said mixture of
pharmaceutical components; wherein said spectrometer measures
spectroscopic characteristics of the contents of said hopper and
wirelessly sends information regarding said spectroscopic
characteristics to said processing device, and said processing
device derives, from said spectroscopic information, information
regarding the homogeneity of said mixture of pharmaceutical
components.
63. The apparatus of claim 62, wherein each of said at least one
detector is configured for detecting a respective wavelength of
light.
64. The apparatus of claim 1, further comprising at least one
second spectrometer and wherein said spectrometer and each of said
at least one second spectrometer include a respective light source
for irradiating a portion of said contents of said hopper at a
respective position.
65. The apparatus of claim 64, wherein said spectrometer and each
of said at least one second spectrometer are disposed at a
respective position on said hopper.
66. The apparatus of claim 65, wherein each of said respective
position is at a respective longitudinal level of said hopper so as
to enable a determination of stratification in said mixture.
67. The apparatus of claim 64, wherein each said light source
includes a respective individual optical fiber of a common fiber
optic bundle light source.
68. The apparatus of claim 67, further comprising a filter device
for restricting passage of light from the common fiber optic bundle
light source through said filter to a predetermined wavelength or
range of wavelengths.
69. The apparatus of claim 64, wherein said spectrometer and each
of said at least one second spectrometer include a respective
detector for detecting respective radiation reflected off or
transmitted through said mixture.
70. The apparatus of claim 64, wherein each of said respective
light source are disposed at a respective position in a neck region
of said hopper.
71. The apparatus of claim 70, wherein each of said respective
light source includes a near-infrared light emitting diode.
72. The apparatus of claim 70, further comprising a plurality of
detectors disposed in said neck region for detecting light
reflected off or transmitted through said mixture.
73. The apparatus of claim 72, wherein the plurality of detectors
are each configured for detecting a respective wavelength of
light.
74. An apparatus for detecting the homogeneity of a pharmaceutical
mixture, the apparatus comprising: a hopper for containing a
mixture of two or more pharmaceutical components, said hopper being
situated within a production line of preparation of a
pharmaceutical dosage form from said mixture; a spectrometer
mounted to said hopper, the spectrometer measuring spectroscopic
characteristics of the contents of said hopper, said spectrometer
comprising a light source emitting radiation in multiple
wavelengths for irradiating said contents of said hopper and at
least one detector for detecting radiation reflected off or
transmitted through said mixture; at least one linear variable
filter for restricting passage of light through said filter in only
a specific predetermined range of wavelengths; a solid state
translation device operatively connected to said at least one liner
variable filter and configured for moving said at least one linear
variable filter; and a processing device not physically coupled to
said spectrometer, said processing device being adapted to analyze
information regarding said spectroscopic characteristics of said
hopper contents and derive therefrom information regarding the
homogeneity of said mixture of pharmaceutical components; wherein
said spectrometer measures spectroscopic characteristics of the
contents of said hopper and wirelessly sends information regarding
said spectroscopic characteristics to said processing device, and
said processing device derives, from said spectroscopic
information, information regarding the homogeneity of said mixture
of pharmaceutical components.
75. The apparatus of claim 74, wherein said at least one detector
comprises a plurality of detectors.
76. The apparatus of claim 74, wherein said solid state translation
device is a piezoelectric bimorph.
77. The apparatus of claim 76, further comprising a lever device
coupling said piezoelectric bimorph to said at least one linear
variable filter and configured for amplifying a movement of said at
least one linear variable filter relative to a movement of said
piezoelectric bimorph.
Description
FIELD OF THE INVENTION
The present invention relates generally to the detection of the
homogeneity of a mixture of components.
BACKGROUND OF THE INVENTION
Pharmaceutical raw materials may be plant, animal or other
biological products; inorganic elements and compounds; or organic
compounds. If the raw material is the subject of a monograph in a
pharmacopoeia or national formulary, a minimum acceptable degree of
chemical purity is specified in order to ensure consumer safety.
Pharmaceutical compositions, which usually include any number of
separate components, including the active drug, are typically mixed
into a homogeneous mixture. Public safety requires assurance of
accuracy in dosages of pharmaceutical medication, and any blending
operation of pharmaceutical raw materials generally seeks to
achieve complete uniformity and homogeneity.
A hopper may be used to feed pharmaceutical raw material into a
mixing device, such as a blender, where the drug is mixed with
other ingredients, generally non-pharmaceutically-active components
known as excipients, in order to form a dosage form such as a
tablet or capsule. During this process, the drug is mixed with
suitable excipients such as dextrin, lactose, salt, polymers,
celluloses, stearic acid, talc, or other inactive ingredients. The
dosage unit can then be packaged as is, or it may be further
modified into a more convenient form for administration to a
patient, such as a capsule or tablet.
A tableting or encapsulating machine may be used to form the
capsule or tablet dosage form. Hoppers can also be used to feed the
pharmaceutical raw material (which may be in the form of a
granulate or dry blend) into a tableting/encapsulating machine.
However, vibrations that occur during the manufacturing process may
cause stratification of the granules within the hopper prior to
preparation of the dosage form. Stratification is localized areas
of differing drug potencies, and may occur even though the
composition within a localized area is itself homogeneous.
Stratification may be related to, varying particle size. A
consequence of stratification may be a dosage form being prepared
with an inaccurate dosage (e.g., a sub-potent or a super-potent
product). Accordingly, the mixing of pharmaceutical compositions is
a crucial step in processing an active drug into a dosage form.
Generally, the homogeneity of a pharmaceutical composition refers
to the distribution of the active drug in the pharmaceutical
composition, and the potency of a pharmaceutical composition refers
to the amount of the active component in the pharmaceutical
composition. Traditionally, the determinations of the homogeneity
and potency of a pharmaceutical mixture have been time consuming.
In addition, traditional methods measure the homogeneity and
potency only of the active component in a pharmaceutical
composition and give no information concerning the homogeneity of
the non-active components.
It is also important to determine the concentration of the other,
non-active components within the pharmaceutical mixture. The
concentration of the non-active components in a pharmaceutical
mixture is important because it determines the physical properties
of the mixture. For example, disintegrants affect the rate of
dissolution of a tablet in a recipient's stomach. If the
disintegrant is not homogeneously distributed in the pharmaceutical
mixture, then the resulting tablets may not dissolve at a uniform
rate, thereby potentially resulting in quality, dosing and
bioavailability problems. Thus, it is important to measure the
homogeneity of all the components of a pharmaceutical mixture
because the dispersion of certain components may ultimately affect
the physical properties of the final form of the pharmaceutical
composition.
Additionally, as noted above, stratification my be associated with
uneven distribution of particle size. The result may be quality,
dosing and bioavailability problems.
One method of determining the homogeneity and potency of a
pharmaceutical mixture involves removing samples of the mixture
from various locations along the path of preparation of the
pharmaceutical mixture, such as the hoppers and blender, and
analyzing these samples for homogeneity and potency. In doing so, a
technician must first stop the process, remove samples of the
composition mixture and assay those samples in a laboratory. The
samples are typically analyzed using a technique such as
ultra-violet (UV) spectroscopy or High Performance Liquid
Chromatography (HPLC) to determine whether the active
pharmaceutical component is uniformly dispersed (is homogeneous) in
the mixture and present at an appropriate concentration level. This
information reflects the potency of the mixture, and, if the
potency of each sample is the same, then the mixture is considered
to be homogeneous. However, neither UV nor HPLC analysis
establishes the concentration of the non-active components of the
mixture. Furthermore, while the samples are taken to the laboratory
and analyzed, the blending or dosage formulation process must be
put on hold.
Alternatively, infrared spectroscopy, which can be useful in
measuring the molecular composition of pharmaceuticals, can also be
used to determine the homogeneity and potency of the ingredients of
a pharmaceutical mixture. Infrared radiation (IR) may be roughly
divided into three wavelength bands: near-infrared radiation,
mid-infrared radiation, and far-infrared radiation. Near-infrared
radiation (NIR) is radiation having a wavelength between about 750
nm and about 3000 nm. Mid-infrared radiation (MIR) is radiation
having a wavelength, between about 3000 nm and about 10,000 nm.
Far-infrared radiation (FIR) is radiation having a wavelength
between about 10,000 nm and about 1000 .mu.m (1000 .mu.m being the
beginning of the microwave region). The desired range may be chosen
to suit the analysis being performed.
In general spectrometers (e.g., spectrophotometers) can be divided
into two classes: transmittance spectrometers and reflectance
spectrometers. In a transmittance spectrometer, light is directed
onto a sample, and a detector detects the light which was
transmitted through the sample. In contrast, in a reflectance
spectrometer, light is directed onto a sample and one or more
detectors detect the light which was reflected from the sample.
Depending upon its design, a spectrometer may, or may not, be used
as both a transmittance and a reflectance spectrometer.
One method of determining the homogeneity and potency of the
components of a pharmaceutical mixture using infrared spectrometry
is shown in U.S. Pat. No. 5,504,332 to Richmond et al., which
purports to disclose a system that uses near infrared technology
for analyzing the uniformity and mass balance of the pharmaceutical
mixture in order to control the tablet manufacturing process. The
system has a library consisting of near infrared spectral scan data
of pharmaceutical materials spanning the normal process range. The
patent states that the assessment of uniformity of a sample mixture
is accomplished by comparison of near infrared spectral information
regarding the sample with the library of near infrared spectral
scans of acceptable material. However, the pharmaceutical material
is not subjected to near infrared analysis while the pharmaceutical
material is being manufactured. Rather, it is analyzed in a
separate device, e.g, as a tablet or as a sample.
Another method of determining the homogeneity and potency of the
components of a pharmaceutical mixture using infrared spectrometry,
although only during active mixing within a blender, is shown in
U.S. Pat. No. 5,946,088 to Aldridge, which purports to disclose an
apparatus for detecting the homogeneity and potency of a mixture of
compositions of matter during the mixing process using a
spectrometer. The described apparatus has a V-shaped container that
rotates about a horizontal axis of rotation during the mixing
process, and the wall of the container includes a single aperture
at the location in the wall intersecting the axis of rotation of
the container. The patent describes that a radiation detector for
detecting spectroscopic characteristics of the mixture is rotatably
mounted through the inside of a hollow shaft about which the
container rotates, and connections to a remote spectroscopic means
and computer, including a fiber optic bundle, are made through the
rotational shaft. The computer synchronizes the taking of
spectroscopic data by the detector with a predetermined single
rotational position or multiple rotational positions of the
container, as the taking of spectral data at a consistent
predetermined point in the rotation of the container, according to
this patent, assures a greater degree of accuracy in determining
the homogeneity of the mixture being mixed.
SUMMARY OF THE INVENTION
Prior art devices use infrared spectrometers that transmit their
data measurements of the molecular composition of pharmaceuticals
by a physical connection, rather than by a wireless one. Thus, such
spectrometers remain physically connected to devices that interpret
the data and to devices that contain the pharmaceutical mixtures.
The necessity of such a physical connection increases the number of
devices necessary to analyze the spectral data and increases the
complexity of the device that prepares the pharmaceutical dosage
form.
In wireless transmissions of data, i.e., when the transmission of
data does not use a physical connection (such as copper cable or
fiber optics), electromagnetic radiation is useful to transmit
information over long distances without damaging the information
due to noise and interference. Various techniques for digital
transmission of data are known in the art. Typically, the desired
information is encoded into a digital signal and then may be
modulated onto a carrier wave and made part of a larger signal. The
signal is then sent into a multiple-access transmission channel,
and electromagnetic radiation, e.g., radio, infrared, and visible
light, is used to send the signal. After transmission, the above
process is reversed at the receiving end, and the information is
extracted. Wireless data transmission may be, for example, via
radio waves or via visible, IR or NIR optical link. Examples of
wireless data transmission via radio waves include cellular phones,
wireless LAN and microwave transmission. Examples of wireless data
transmission via visible or NIR optical link include remote
controls for televison and wireless data ports of laptop computers
and personal digital assistants (PDAs).
None of the prior art systems provide an apparatus for wirelessly
determining the homogeneity and potency of the components of a
pharmaceutical mixture immediately prior to preparation of the
dosage form. Moreover, none of the prior art systems described
above provide an apparatus for determining the potency of the
components of a pharmaceutical mixture while the pharmaceutical
mixture is in a hopper. Accordingly, it is desirable to provide an
apparatus that can assess the homogeneity and potency of the
components of a pharmaceutical mixture in a hopper, detect
stratification or non-uniformity of the mixture of the components
immediately prior to preparation of the dosage form from the
pharmaceutical mixture, and transmit this information wirelessly to
a computer for analysis.
In accordance with a preferred embodiment of the invention, an
apparatus is provided for detecting the homogeneity of a
pharmaceutical mixture. The apparatus has a hopper that is situated
within a production line of preparation of a pharmaceutical dosage
form. The hopper contains a mixture of two or more pharmaceutical
components. The mixture may, for example, be a granulation or a dry
blend. A spectroscopic device (e.g., a spectrometer) is mounted to
the hopper for measuring spectroscopic characteristics of the
contents of the hopper. A processing device can be situated remote
from and not physically coupled to the spectroscopic device, the
processing device being adapted to analyze information regarding
said spectroscopic characteristics of the mixture and derive
therefrom information regarding the homogeneity and/or
stratification of the mixture. The spectroscopic device measures
the spectroscopic characteristics of the mixture within the hopper
and wirelessly sends this information to the remote processing
device, which derives information regarding the homogeneity and/or
stratification of the mixture of pharmaceutical components. The
wireless transmission of the spectroscopic characteristics can be
done through infrared radiation or near infrared radiation, and the
spectroscopic characteristics can be converted to digital signals
prior to being transmitted. The preferred embodiments of this
invention contemplate various configurations of the source of light
or radiation, the detectors and the filtering devices, as well as
various different and specific types of sources of light or
radiation, detectors and the filtering devices.
In accordance with certain embodiments of the present invention,
the spectroscopic device (e.g., a spectrometer) comprises at least
one linear variable filter moved by a piezoelectric bimorph
relative to a light source, such that said mixture in the hopper is
irradiated with radiation in at least one specified band of
wavelengths corresponding to the position of said at least one
linear variable filter relative to said light source. In accordance
with other aspects of this embodiment, the at least one variable
filter includes a plurality of variable filters, and the detector
includes a plurality of detectors, each of the plurality of
variable filters passes light in a different band of wavelengths,
each of the plurality of variable filters being associated with a
corresponding one of the plurality of detectors.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A shows a schematic representation of a first embodiment of
the present invention in a pre-dispersive configuration.
FIG. 1B illustrates a schematic representation of a first
embodiment of the invention in a post-dispersive configuration.
FIG. 1C illustrates a schematic representation of a first
embodiment of the invention in a configuration that uses a
monochromatic source of light and no filter.
FIG. 1D illustrates a schematic representation of a first
embodiment of the invention wherein the light source and detector
are configured for a transmittance measurement.
FIG. 1E shows a schematic representation of a first embodiment of
the invention wherein the light source and detector are mounted
inside the hopper.
FIG. 1F shows a schematic representation of a first embodiment of
the invention wherein the light source and detector are configured
for a reflectance measurement.
FIG. 1G shows a schematic representation of an embodiment of the
present invention wherein the granulation follows a path from the
input of the hopper to the output of the hopper.
FIG. 1H shows a schematic representation of another embodiment of
the present invention.
FIG. 2 shows a schematic representation of a second embodiment of
the invention in a mode wherein the processing device is physically
connected to spectrometer.
FIG. 3 shows a schematic representation of a third embodiment of
the present invention wherein a plurality of spectrometers or
transparent elements are used.
FIG. 4 shows a schematic representation of an embodiment of the
present invention wherein a fiber optic bundle is used as a light
source for illuminating multiple positions.
FIG. 5 shows a schematic representation of an embodiment of the
present invention wherein in a single detector is interfaced to
multiple fiber optic light guides.
FIG. 6 shows a schematic representation of an embodiment of the
present invention wherein the spectrometer transparent element is
disposed on a top surface of a hopper valve.
FIG. 7 shows a schematic representation of a configuration for
transmitting the digital signal to a processor.
FIG. 8 shows a schematic representation of another configuration
for transmitting the digital signal to a processor.
FIG. 9 shows a schematic representation of a networking arrangement
for transmitting the digital signal in accordance with another
embodiment of the present invention.
FIG. 10 shows a schematic representation of another embodiment of a
networking arrangement for transmitting the digital signal.
FIG. 11 shows a schematic representation of a networking
arrangement for transmitting the digital signal in accordance with
yet another embodiment of the present invention.
FIG. 12 shows a schematic representation of still another
networking arrangement for transmitting the digital signal.
FIG. 13 shows a schematic representation of a further networking
arrangement for transmitting the digital signal.
FIGS. 14A B show an illustrative remote spectrometer for performing
spectral scans.
FIGS. 15A B illustrate spectroscopic detector arrangements.
FIG. 16 illustrates the manner in which a remote wireless
spectrometer can interact with a central computer.
FIG. 17 illustrates in more particular detail the elements of a
base connection to the main computer.
FIGS. 18A F show a further preferred embodiment of a remote
spectrometer.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1A shows a schematic representation of a first embodiment of
the present invention in a pre-dispersive configuration. One or
more substances (which, may for example, be a granulation 6, a
mixture or a pharmaceutical component) are fed into a hopper 10.
Hopper 10 can be any one of the many different types of hoppers
known to those skilled in the art, such as those manufactured by
N.K. Engineering Co., or a hopper feeder, such as those
manufactured by Garvey Corporation. The hopper 10 can be located in
a production line comprising a mixer, a tableting press, and/or an
encapsulating press. For example, the hopper can be located
upstream of the mixer to feed a pharmaceutical mixer to the mixer,
and/or upstream of a tableting (or an encapsulation press to feed a
pharmaceutical mixer to the press. In certain embodiments, the
hopper can be integrated into mixer, tableting press, and/or
encapsulating.
In general, hopper 10 may have a valve 12 to accumulate a set
amount of the granulation 6, or, if the substances fed into the
hopper is a mixture of powders, a dry blend. It should be
appreciated that although the end product discharged from the
hopper 10 is referred to in the following discussion as granulation
6, it can be any conventional end product of a hopper, including,
for example, a dry blend. Valve 12 can also be a knife valve or a
butterfly valve, such as an ultra-sanitary butterfly valve made by
Cobra International, to also prevent jamming and sticking of
granulation 6 within hopper 10. In one embodiment, after
granulation 6 has reached a pre determined volume, granulation 6
passes into a tableting/encapsulating machine 15.
Tableting/encapsulating machine 15 can be any of the known machines
in the art, such as a single rotary tableting machine, a double
rotary tableting machine, a GMP rotary tableting machine (for
example, manufactured by Gaylord), a Slugging/Bolus press, a high
speed tablet press, an oscillating granulator (for example,
manufactured by Victory Enterprises), etc. In certain embodiments,
the present invention may use tablet presses, such as those
manufactured by Niro Inc., Se Jong Machinery Co. or Cadmach. In
certain other embodiments, hopper 10 forms a part of
tableting/encapsulating machine 15.
A spectrometer (which is shown schematically at 20) is mounted to
hopper 10. A variety of different types of spectrometers are known
in the art, such as grating spectrometers, FT (Fourier
transformation) spectrometers, Hadamard transformation
spectrometers, AOTF (Acousto Optic Tunable Filter) spectrometers,
diode source spectrometers, filter-type spectrometers, scanning
dispersive spectrometers, nondispersive spectrometers, and others
as discussed below, and any of these may be used with the present
invention.
In certain embodiments, a plurality of spectrometers 20 may be
mounted to the hopper 10. Referring to FIG. 1(g), granulation 6
follows a path 1000 (preferably a vertical path as shown) from the
input 1010 of the hopper 10 to the output 1020 of the hopper. The
plurality of spectrometers 10 can be mounted to the hopper in
various configurations. For example, the spectrometers can be
mounted along a plane 1001 perpendicular to the path 1000 as
described below with regard to FIG. 3 to determine whether the
homogeneity and/or moisture content of the granulation varies at a
particular level of the hopper 10. Alternatively, the spectrometers
can be spaced apart along the path 1000 (e.g., vertically spaced
apart) to determine whether the homogeneity and/or moisture content
of the granulation varies at different points along the path
1000.
Filter-type spectrometers, for example, utilize a light source
(e.g., tungsten filament lamp) to illuminate a rotating opaque
disk, wherein the disk includes a number of bandpass optical
filters or beam splitters. The disk is then rotated so that each of
the bandpass filters passes between the light source and the
sample, and an encoder indicates which optical filter is presently
under the light source. The filters interact with the light from
the light source so that only a selected wavelength range passes
through the filter to the sample. Optical detectors are positioned
to detect light which either is reflected by the sample (to obtain
a reflectance spectra) or is transmitted through the sample (to
generate a transmittance spectra). The amount of detected light is
then measured, thereby providing an indication of the amount of
absorbance of the light by the sample.
Diode Source spectrometers use infrared emitting diodes (IREDs) as
sources of near infrared radiation. A plurality (for example,
eight) of IREDs are arranged over a sample work surface to be
illuminated for quantitative analysis. Near-infrared radiation
having a narrow bandwidth (e.g. 30 50 nm) emitted from each IRED
impinges upon an accompanying optical filter. Each optical filter
is a narrow bandpass filter which passes NIR radiation at a
different wavelength. NMR radiation passing through the sample is
detected by a detector (such as a silicon photodetector). The
amount of detected light is then measured, thereby providing an
indication of the amount of absorbance of the light by the
substance under analysis.
Acousto Optical Tunable Filter spectrometers utilize a radio
frequency (RF) signal to generate acoustic waves in a TeO.sub.2
crystal. A light source transmits a beam of light through the
crystal, and the interaction between the crystal and the RF signal
splits the beam of light into three beams: a center beam of
unaltered white light and two beams of monochromatic and
orthogonally polarized light. A sample is placed in the path of one
of the monochromatic beam detectors, which are positioned to detect
light that either is reflected by or transmitted through the
sample, and the amount of detected light is then measured, thereby
providing an indication of the amount of absorbance of the light by
the sample. The wavelength of the light source can be incremented
across a wavelength band of interest by varying the RF
frequency.
In grating monochromator spectrometers, a light source transmits a
beam of light through an entrance slit and onto a diffraction
grating (the dispersive element) to disperse the light beam into a
plurality of beams of different wavelengths (i.e., a dispersed
spectrum). The dispersed light is then reflected back through an
exit slit onto a detector. By selectively altering the path of the
dispersed spectrum relative to the exit slit, the wavelength of the
light directed to the detector can be varied. The amount of
detected light is then measured, thereby providing an indication of
the amount of absorbance of the light by the sample. The width of
the entrance and exit slits can be varied to compensate for any
variation of the source energy with wave number.
In an ATR (attenuated total reflectance) spectrometer, radiant
energy incident on an internal surface of a high refractive index
transparent material is totally reflected. When an infrared
absorbing material is in optical contact with the totally
internally reflecting surface, the intensity of the internally
reflected radiation is diminished for those wavelengths or energies
where the material absorbs energy. Since an internal reflecting
surface is essentially a perfect mirror, the attenuation of this
reflected intensity by a material on its surface provides a means
of producing an absorption spectrum of the material. Such spectra
are called internal reflection spectra or attenuated total
reflection (ATR) spectra.
The material with the high index of refraction that is used to
create internal reflection is called an internal reflection element
(IRE) or an ATR crystal. The attenuation of the internally
reflected radiation results from the penetration of the
electro-magnetic radiation field into the matter in contact with
the reflection surface. This field was described by N. J. Harrick
(1965) as an evanescent wave. It is the interaction of this field
with the matter in contact with the IRE interface that results in
attenuation of the internal reflection. Though not absolutely
necessary, pressure on an ATR crystal may improve performance by
increasing the amount of the substance (e.g. granulation 6) that is
in contact with the IRE. Pressure may be generated by placing the
crystal in neck region 98 of hopper 10, where higher pressure
exists due to the weight of granulation 6 above. Alternatively, the
ATR crystal may be mounted on a piston device that presses into
granulation 6 when in a forward position so that the crystal only
scans when in this forward position.
Any such spectrometer may be suitably used with the present
invention. In one embodiment, as shown in FIGS. 1A E, an aperture
or window 16 is formed through a wall 11 of hopper 10, and
spectrometer. 20 is mounted to hopper 10 about aperture or window
16. In certain embodiments, a transparent element 25 such as a
lens, can be located outside hopper 10 as part of spectrometer 20
and can serve to focus and/or direct light onto granulation 6
within hopper 10. In other embodiments, transparent element 25 is
fit into a slit or indentation in wall 11 of hopper 10 adjacent to
window 16 or, alternatively, can be used instead of window 16. In
an ATR embodiment of the present invention, the window 16 can
function as the internal reflection element.
Referring to FIG. 1H, in a further embodiment of the present
invention, a plurality of IREs 25.1 25.4 are secured to the
interior surface of the hopper. In this embodiment, each IRE
extends laterally across the interior surface of the hopper 10.
Preferably, each IRE extends substantially across the entire
circumference (in the case of a circular or elliptically shaped
interior surface), or substantially across each interior wall (in
the case of an interior surface shaped as a polygon) of the hopper
10, and the IRE's 25.1 25.4 are vertically spaced apart. In this
manner, each IRE will detect the average spectroscopic
characteristics of the substance at its corresponding vertical
level. By comparing the detected spectroscopic characteristics of
IRE's 25.1 through 25.4, differences in homogeniety and/or moisture
in different portions of the hopper can be determined. Examples of
suitable IRE's include various fused silica know to be effective in
the infrared region.
In one preferred embodiment, spectrometer 20 has a light source 21,
a light filtering device 23, a transparent element 25 and a
detector 26. Light source 21 generates a beam of light or radiation
that passes through light filtering device 23. Light filtering
device 23 separates the beam of polychromatic light into a
monochromatic beam (or a beam having a narrower band of wavelengths
than the polychromatic beam that is generated by light source 21
has), which then passes through a transparent element 25, such as a
lens, that is set within or adjacent to window 16 in wall 11 of
hopper 10, as illustrated in FIG. 1A. After passing through
transparent element 25, the beam of light or radiation impinges on
granulation 6. The reflected light is then absorbed by detector 26,
which converts the detected beam of radiation (which now comprises
the spectroscopic characteristics of the material in the hopper 10)
into a digital signal. In an embodiment of the present invention
utilizing an ATR spectrometer, the transparent element 25 can be
the IRE and the beam could reflect off the interface between
granulation 6 and spectrometer transparent element 25 (e.g., where
the granulation 6 and transparent element 25 contact one another).
This configuration of the embodiment of FIG. 1A is "pre-dispersive"
because the light generated by light source 21 passes through light
filtering device 23 and is filtered to a monochromatic beam prior
to it being dispersed by or reflected off the substance being
analyzed, i.e., granulation 6.
In certain embodiments, detector 26 can be a photographic plate, a
photoemissive detector, an imaging tube, a solid-state detector or
any other suitable detector. Light filtering device 23 can be a
prism, a grating filter (which is an optical device with a surface
ruled with equidistant and parallel lines for the purpose of
filtering light), an interferometer, or any other suitable filter.
In an FTIR embodiment, a beam splitter and a movable mirror can be
incorporated into spectrometer 20.
Preferably, spectrometer 20 and transparent element 25 are located
above valve 12, either at a position adjacent to window 16 or at a
position adjacent to window 17, as shown in FIG. 1A, or elsewhere
suitable. However, in certain embodiments, spectrometer 20 can be
located below valve 12. Wherever spectrometer 20 is located,
embodiments utilizing a single spectrometer can be useful for
collecting spectra from a "sample stream" of granulation 6 as it
passes by transparent element 25. In addition, in a multiple
reading embodiment of the invention, wherein multiple spectroscopic
scans of the composition are taken, some of a plurality of
spectrometers 20 or transparent elements 25 can be placed above
valve 12, while others can be placed below valve 12. In the
multiple reading embodiment, the different readings taken at
different steps in the process can be compared with each other in
order to locate a problem within the manufacturing process. The
material for the transparent element can be selected as a function
of the desired wavelength to be used. For example, glass is
transparent up to 2200 nm, sapphire is transparent up to 5 microns,
and barium fluoride is transparent up to 20 microns.
In this embodiment, as illustrated in FIG. 1A, spectrometer 20 is
in wireless communication with a processing device 32 (which, in
this example, is a remote processing device) such that spectrometer
20 is capable of wirelessly transmitting spectral data to
processing device 32 at a remote location. In one embodiment,
detector 26 converts the reflected beam into a digital signal that
is then wirelessly transmitted to remote processor 32, where the
reflected beam is analyzed. The digital signal generated by
detector 26 of spectrometer 20 is first fed into a transmitter 30
located in or attached to spectrometer 20 and coupled to detector
26. Transmitter 30 then transmits the digital signal wirelessly to
a receiver 31, which receives the digital signals on behalf of
processing device 32. The digital signal can be transmitted from
transmitter 30 to receiver 31 by any known technique in the
wireless transmission art, as will be discussed in greater detail
below.
FIG. 1B illustrates a schematic representation of the first
embodiment of the invention in a post-dispersive configuration. In
this embodiment, the beam of light generated by light source 21
first impinges upon granulation 6 and only then passes through
light filtering device 23. After passing through light filtering
device 23, the reflected light is absorbed by detector 26. This
configuration is "post-dispersive" because the light generated by
light source 21 passes through light filtering device 23 and is
filtered to a monochromatic beam (or a beam having a narrower band
of wavelengths than the polychromatic beam that is generated by
light source 21 has) after is has been dispersed by or reflected
off the substance being analyzed, i.e., granulation 6
FIG. 1C illustrates a schematic representation of the first
embodiment of the invention in a configuration wherein spectrometer
20 does not comprise a light filtering device 23 at all. In this
embodiment, because light filtering device 23 is not present, light
generated by light source 21 is not passed through a filtering
device either prior to being reflected off granulation 6 or after
being reflected off granulation 6. Instead, light source 21 itself
generates a beam of monochromatic light. Light source 21 can thus
be, for example, a monochromatic laser.
FIG. 1D illustrates a schematic representation of a first
embodiment of the invention wherein light source 21 and detector 26
of spectrometer 20 are configured for a transmittance measurement.
Light source 21 generates a beam of light, which passes through
light filtering device 23 and onto granulation 6. Transparent
element 25 can also be included within this configuration, in order
to focus or direct light onto granulation 6. The beam of light then
impinges detector 26, where the spectral data is measured.
Alternatively, filtering device 23 could be situated adjacent to
detector 26 (not shown), rather than adjacent light source 21, so
that filtering of the light beam is performed post-dispersively,
rather than pre-dispersively, as shown in FIG. 1D. Detector 26 can
be situated inside wall 11 of hopper 10 (not shown) or outside wall
1, in which case light would exit hopper 10 through window 16'.
Whether light filtering device 23 is located adjacent to light
source 21 or to detector 26, filtering device 23 and/or transparent
element 25 could alternatively form a portion of wall 11 of hopper
10. In this embodiment, detector 26 may communicate with
transmitter 30 or processing device 32 by a physical connection
(e.g., a copper wire) or wirelessly, as discussed below.
FIG. 1E shows an embodiment of the invention in a variation of FIG.
1D wherein the positions of light source 21 and detector 26 are
effectively reversed. In this embodiment, light source 21 is still
situated on the opposite side of hopper 10 from detector 26 in
order to facilitate transmittance spectrometry. As shown in FIG.
1E, however, detector 26 is located adjacent to spectrometer 20. In
one version of this embodiment, both light source 21 and detector
26 can be mounted inside hopper 10, most preferably on opposite
sides of hopper 10. Window 16 need not be present in this version
of the embodiment, since light source 21 is inside hopper 10, and
light generated by light source 21 passes through granulation 6
prior to being detected by detector 26. As shown in FIG. 1E,
detector 26 maybe mounted outside wall 11 of hopper 10, within
spectrometer 20, or behind window 16 in wall 11.
FIG. 1F shows a schematic representation of a first embodiment of
the invention, in a side view of hopper 10, wherein light source 21
and detector 26 are configured for a reflectance measurement. Light
source 21 generates a beam of light, which passes through light
filtering device 23 and onto granulation 6. No transparent element
25 is used. A portion of the beam of light reflected off the
granulation 6 continues onto detector 26, where the spectral data
is measured.
FIG. 2 illustrates a second embodiment of the invention in a mode
wherein processing device 32 is physically connected to
spectrometer 20, rather than being remotely separated therefrom, as
shown in FIGS. 1A 1F. In this embodiment, detector 26 converts the
reflected beam into a digital signal that is then transmitted to
processor 32 that is physically within, attached to or adjacent to
spectrometer 20, where the reflected beam is analyzed. The
connection between processing device 32 and detector 26 can be by
conventional cables, wires or data buses, in which case
transmission takes place through such physical connections. In this
embodiment, there is no need for the digital signal generated by
detector 26 to be fed into a transmitter located in or attached to
spectrometer 20 and then transmitted wirelessly to a receiver on
behalf of processing device 32.
However, a transmitter 30 may still be present and located in or
attached to spectrometer 20 and coupled to processor 32. The
digital signal that is analyzed and/or transformed by processing
device 32 can be then fed to transmitter 30 for transmission to
receiver 31 via a wireless connection. Transmitter 30 transmits the
digital signal of data processed by processing device 32 wirelessly
to receiver 31, which receives the digital signals on behalf of a
remote processing device 38 for further processing. As before, the
digital signal can be transmitted from transmitter 30 to receiver
31 by any known technique in the wireless transmission art, as will
be discussed in greater detail below. Processing device 32 may
compress the digital signal so that it can be transmitted more
efficiently or may modify the digital signal to facilitate error
correction/detection, such as by inserting hamming code bits or
error checking bits into the digital signal. The receiver can be
physical connected to other devices (e.g., another processing
device or display device).
FIG. 3 shows a third embodiment of the invention wherein a
plurality of spectrometers 20 or transparent elements 25 are
disposed about the circumference of hopper 10 (e.g., along the
plane 1001 of FIG. 1G). In this embodiment, each transparent
element 25 can be optically connected to a separate spectrometer
20. Thus, spectroscopic scans of the composition at different
positions or angles in hopper 10 can be taken. In this embodiment,
each of the plurality of spectrometers 20 situated about the
circumference of hopper 10 can be any of the embodiments discussed
above, and as shown in FIGS. 1A 1F and 2, or as discussed below.
Thus, the various spectrometers can derive data regarding
granulation 6 through may variations and embodiments, so as to
obtain readings that are verifiably accurate though various
different techniques.
With further reference to FIG. 3 and FIGS. 1A and 1B, in an
embodiment of the present invention, plurality of spectrometers 20
may be located in neck region 98 of hopper 10, so that light
sources 21 flood the neck region with large amounts of light. A
"ring light" may thus be provided. Large amounts of light provide a
relatively large signal-to-noise ratio for spectral analysis
purposes. Such an embodiment would be especially useful for
analyzing the homogeneity of granulation 6. Light sources 21 could
be NIR light emitting diodes (LEDs), for example, since such
devices generate relatively little heat. Detectors 26 for each
spectrometer 20 may be diode arrays or linear variable filter
detectors (such as the MicroPac family of products available from
OCLI), for example. Alternatively, detectors 26 could each include
a number of individual diodes having a respective filter 23 for
excluding all but a desired wavelength of light, as in the
embodiment shown in FIG. 1B. In this way, intensity values at
different wavelengths may be measured for each position on hopper
10. In other embodiments of the present invention, a fiber optic
bundle split into individual optical fibers, as shown in FIG. 4
below, could be used as the light source for flooding neck region
98 with light.
FIG. 4 shows another embodiment of the invention wherein a
plurality of spectrometers 20 or transparent elements 25 are
disposed about the circumference of hopper 10. This embodiment may
be especially useful for analyzing for stratification in
granulation 6. In this embodiment, light source 21 includes fiber
optic bundle 92 optically connected to filtering, or monochromator,
device 23. Filtering device 23 may be a grating, interferometer,
filter wheel, or other suitable device for producing a
monochromatic beam of light in each fiber of fiber optic bundle 92.
Splitter device 94 is provided for splitting fiber optic bundle 92
into a plurality of individual fibers 96, which illuminate
respective multiple positions, or angles, in hopper 10 via
respective transparent elements 25. Respective detectors 26 are
provided at each position or angle in hopper 10 for detecting light
diffusively reflected, transmitted, etc., from granulation 6. Any
desired number of spectrometers 20, and hence, of illumination and
detection (sampling) positions on hopper 10, may be provided
situated in a desired configuration about the circumference of the
hopper. Moreover, the spectrometers may be positioned at different
longitudinal levels on hopper 10, as shown in FIG. 4.
FIG. 5 shows an embodiment of the invention having a single
spectrometer 20 with a plurality of transparent elements 25
disposed as different longitudinal levels about the circumference
of hopper 10. This embodiment, like the embodiment shown in FIG. 4,
may be especially useful for analyzing for stratification in
granulation 6. In this embodiment, like that shown in FIG. 4 and
discussed above, light source 21 including fiber optic bundle 92 is
provided. Fiber optic bundle 92 is optically connected to
filtering, or monochromator, device 23. Filtering device 23 may be
a grating, interferometer, filter wheel, or other suitable device
for producing a monochromatic beam of light in each fiber of fiber
optic bundle 92. Splitter device 94 is provided for splitting fiber
optic bundle 92 into plurality of individual fibers 96, which
illuminate respective multiple positions, or angles, in hopper 10
via respective transparent elements 25.
In the embodiment shown in FIG. 5, single detector 26 is provided.
Detector 26 maybe a photo diode array or a single element detector
combined with a monochromator interferometer, for example.
Switching device 93 interfaces detector 26 with fiber optic light
guides 95, each connected to a respective sampling position 97 at a
respective transparent element 25. Each fiber optic light guide 95
receives diffusively reflected or transmitted, etc., light from
granulation 6. Switching device 93 selects one sampling position 97
at a time and presents the received light to detector 26. This
embodiment may be used to read out each sampling position 97 in a
desired sequence in a relatively short period of time. Any desired
number of sampling positions 97 may be provided situated in any
desired configuration about hopper 10. In other embodiments of the
present invention (not shown) respective individual light sources
21 may be provided for each transparent element 25, instead of
using splitter device 94 plurality of individual fibers 96.
FIG. 6 shows a fourth embodiment of the invention wherein
spectrometer transparent element 25 is embedded in the top surface
of valve 12. In an embodiment using an ATR spectrometer, the
transparent element 25 can be the IRE.
As stated above, the digital signal can be transmitted from
transmitter 30 to receiver 31 by any known technique in the
wireless transmission art, such as transmission using carrier waves
in the IR, radio, optical or microwave region of the wavelength
spectrum. Infrared (IR) transmission uses an invisible portion of
the spectrum slightly below the visible range. The IR transmission
can be directed, which requires a direct line-of-site, or diffuse,
which does not require line of sight.
Radio transmission uses the radio region on the spectrum, which is
located above the visible portion of the spectrum. Suitable devices
that allow digital signals to be transmitted in the FM radio region
of the spectrum are made by Aeolus and Xircon. In certain
embodiments, Xircon's Core Engine can be directly embedded in the
electronics of transmitter 30 and receiver 31. In certain
embodiments, transmitter 30 and receiver 31 can be linked to a
Wi-Fi certified wireless network anywhere in the world, and
GSM/CDMA, LAN and WAN connections can also be provided, using
devices provided, for example, by 3Com or Nokia.
The digital signal may also be wirelessly transmitted from
transmitter 30 to receiver 31 in the microwave frequencies, which
are located below the visible range of the spectrum. Nokia
microwave radios, for example, can provide a microwave link between
transmitter 30 and receiver 31.
Optical devices, such as those based on lasers, can also be used to
transmit the digital signal from transmitter 30 to receiver 31.
Once receiver 31 receives the digital signal from transmitter 30.
Receiver 31, in turn, transmits the digital signal to a processing
device 32 to which it is coupled, by any known method. Processing
device 32 can be physically coupled to receiver 31, as illustrated
in FIG. 1A such as through conventional cables, wires or data
buses, in which case such transmission takes place through such
physical connections. Processing device 32 can also be separate
from receiver 31 and coupled thereto wirelessly, in which case such
transmission from receiver 31 to processing device 32 takes place
through any of the wireless methods discussed above. Upon receipt
of the digital signal from receiver 31, processing device 32 can
then process the digital signal as well as transmit the digital
signal to peripherals, such as a display device 33 and/or storage
device 34. In a network embodiment, processing device 32 can
transmit the digital signal to subsequent processing devices. In
the embodiment shown in FIG. 2, for example, processing device 32
can transmit the signal to a further remote device 38, which can
transmit the digital signal to peripherals, such as a display
device 33 and/or storage device 34.
The communication between spectrometer 20, receiver 31 and the
processing device 32 in FIGS. 1A 1H (as well as with remote device
38 in FIG. 2) can also be via a wireless peer-to-peer network. In
such a network, spectrometer 20 and attached transmitter 30 send
the digital signal to processing device 32 and receiver 31, which
can, for example, be a laptop PC equipped with wireless adapter
card, via a wireless connection. From processing device 32, a user
can analyze the digital signal, transform the digital signal,
compare the digital signal to the data set in storage device 34 or
display the digital signal on display device 33. Processing device
32 can be moved, so that communication with other spectrometers is
possible without the need for extensive reconfiguration. In this
embodiment, spectrometer 20 and transmitter 30 function as a
client, while processing device 32 acts as a server.
A data reduction technique, such as a partial least squares, a
principal component regression, a neural net, a classical least
squares (often abbreviated CLS, and sometimes called The K-matrix
Algorithm), or a multiple linear regression analysis can then be
used to generate a modeling equation from the digital signal.
In certain embodiments, processing device 32 can use various
algorithms to pre-treat the spectral data prior to modeling the
data via the data reduction technique. For example, a baseline
correction, a normalization of the spectral data, a first
derivative on the spectral data, a second derivative on the
spectral data, a multiplicative scatter correction on the spectral
data, a smoothing transform on the spectral data, a Savitsky-Golay
first derivative, a Savitsky-Golay second derivative, a
mean-centering, Kubelka-Munk transform, and/or a conversion from
reflectance/transmittance to absorbance can be performed. The
pre-treated data signal can be displayed to the user as a
spectrograph (a graphical representation of absorption as it
relates to different wavelengths). One or more of these
above-mentioned treatments can be performed on the data in any
order desired.
A user may select which pre-treatments and/or reduction techniques
to use in transforming or modeling the data. In certain
embodiments, the pre-treatments and/or reduction techniques may
also be selected pursuant to a set of rules specifying which
algorithms to use for a particular type of composition.
FIG. 7 shows a schematic representation of a configuration for
transmitting the digital signal between spectrometer 20 and a
central processing device 36, with multiple processing devices 32
and 35a, 35b, 35c arranged in a distributive network. In this
configuration, spectrometer 20 includes transmitter 30 and
wirelessly transmits a digital signal to receiver 31. The first
processing device 32 (e.g., a routing device) receives the digital
signal from receiver 31 and transmits a first portion of the
digital signal to processing device 35a (e.g., a computer in a
distributive network), a second portion of the digital signal
to-processing device 35b, and a third portion of the digital signal
to processing device 35c. Processing devices 35a, 35b, 35c perform
various functions on their respective portions of the digital
signal in parallel (e.g., transformations of the digital signal)
and then each transmits a modified digital signal to a fifth
processing device 36 (e.g., a personal computer). Processing device
36 analyzes and transmits the digital signal to display device 33
(e.g., a monitor) and to storage device 34 (e.g., a hard disk). The
communication between any of the devices can be via wireless
communication, or the devices can be physically connected (e.g.,
copper wire or fiber optic cable).
Although only one spectrometer 20 with a transmitter 30 is shown in
FIG. 7, an arrangement with a plurality of spectrometers, each
connected to the same processing unit or distributed over the
plurality of processing units, is possible. Similarly, it should be
understood that the present invention is not limited to the number
or configuration of processing devices 32, 35a, 35b, 35c and 36
shown in FIG. 7. Other configurations, with more or fewer
processing devices, are possible.
FIG. 8 shows a schematic representation of another configuration
for transmitting the digital signal to a processor, between a
plurality of processing devices 32 and a central processing device
37. Spectrometer 20 with associated transmitter 30 wirelessly
transmits the digital signal to a receiver 31, which is integrated
within or coupled to one of processing devices 32 and in
communication therewith. Each processing device 32 (e.g., a routing
device) transmits the digital signal either to central processing
device 37 or to a different processing device 32. Central
processing device 37 analyzes the digital signal. Central
processing device 37 processes the digital signal and may also
transmit the digital signal or selected portions of the data
contained therein to display device 33 (e.g., a monitor) where it
is displayed in human readable form. Central processing device 37
may also transmit the digital signal or selected portions therein
to storage device 34 (e.g., a hard disk). The communication between
any of the devices can be via wireless communication (e.g., radio
waves). The devices can also be physically connected (e.g., by wire
or fiber optic cable). Furthermore, central processing unit 37 can
be mobile, such as by being mounted in a mobile platform (e.g., a
laptop or hand-held device) or by itself having a mobile structure,
such as a lap-top computer, so that central processing unit 37 can
be placed at different positions with respect to the network.
Although only one spectrometer 20 with a transmitter 30 is shown in
FIG. 8, an arrangement with a plurality of spectrometers 20, each
connected to the same processing unit or distributed over the
plurality of processing units 32, is possible.
In certain embodiments, transmitter 30 can be a
transmitter/receiver device, so that the spectrometer 20 may
function with a Global Positioning System (GPS). GPS technology
allows tracking of the device and may prove helpful if the
spectrometer is lost or stolen. Furthermore, the GPS coordinates of
hopper 10 can be sent, along with the digital signal, to a central
database, so that, if a problem is detected regarding hopper 10, a
repair technician could be sent directly to the hopper by using the
hopper's GPS coordinates. Thus, a manufacturing plant that
continues to have problems could more easily be ascertained.
FIG. 9 shows a schematic representation of a networking arrangement
for transmitting the digital signal in accordance with another
embodiment of the present invention. The wireless access point 51
can be any suitable device, such as Linksys's WAP 11. Spectrometer
20 wirelessly transmits the digital signal to wireless access point
51 by transmitter 30. Wireless access point 51 then transmits the
digital signal to a router 52 via a physical connection. Router 52
can be any suitable device, such as a Linksys' BEFSR41 4-port
cable/DSL router. Router 52, in turn, transmits the data to
processing device 32 and a cable modem 53. Router 52 can be
connected to processing device 32 and cable modem 53 by any
suitable device, such as, for example, a 10BaseT connector. At
processing device 32, a user may perform functions on the data,
view the data and/or store the data. Cable modem 53 transmits the
digital signal over existing phone lines to a communication
provider 56, e.g., AT&T, which in turn uses existing networks
to transfer the digital signal to the Internet 57. From the
Internet 57, the digital signal is received by another
communication provider 58, e.g., America Online, which transmits
the digital signal to a second wireless access point 54. Second
wireless access point 54 can be any suitable device, such as a
Linksys' WAP11. Provider 58 can be connected to second wireless
access 54 point by, for example, existing phone lines. Second
wireless access point 54 transmits the digital signal to a mobile
processing device 55, such as a laptop computer, equipped with a
wireless card. The wireless card can be any suitable device, such
as, for example, 3Com's Wireless AirConnect PC card. From mobile
processing device 55 with the wireless card or the processing
device 32 a user can perform functions on the digital signal, the
digital signal can be displayed and/or the digital signal can be
stored.
FIG. 10 illustrates a plurality of clients 72 and a plurality of
access points 70 arranged in a wireless network. In this
embodiment, spectrometer 20 and transmitter 30 function as one of
the clients 72. Clients 72 can also be processing device 32 (e.g.,
a PC or a lap-top). Each client 72 can wirelessly transmit the
digital signals to a wired network 71 by transmitting to one of
access points 70. Access points 70 extend the range of the wired
network 71, effectively doubling the range at which the devices can
communicate. Each access point 70 can accommodate one or more
clients 72, the specific number of which depends upon the number
and nature of the transmissions involved. For example, a single
access point 70 can be configured to provide service to fifteen to
fifty clients 72. In certain embodiments, clients 72 may move
seamlessly (i.e., roam) among a cluster of access points. 70. In
such an embodiment, access points 70 may hand client 72 off from
one to another in a way that is invisible to the client 72, thereby
ensuring unbroken connectivity.
Once the digital signal enters wired network 71, the digital signal
can be relayed to a server 75, the display device 73 and the
storage device 74, as well as to other clients 72. Server 75 or
other clients 72 can convert the digital signal to a spectrograph
and/or perform various algorithms on the digital signal.
In certain embodiments, an extension point 79 is provided.
Extension points 79 augment the network of access points 70 and
function like access points 70. However, extension points 79 are
not tethered to wired network 71 as are access points 70. Instead
extension points 79 communicate with one-another wirelessly,
thereby extending the range of network 71 by relaying signals from
a client 72 to an access point 70 or another extension point 79.
Extension points 79 may be strung together in order to pass along
messaging from an access point 70 to far-flung clients 72.
FIG. 11 shows a schematic representation of a networking
arrangement for transmitting the digital signal in accordance with
yet another embodiment of the present invention. Communication
between first and second networks 81,82 is by directional antennas
80a,80b. Each antenna 80a,80b targets the other to allow
communication between networks 81,82. First antenna 80a is
connected to first network 81 via an access point 70a. Likewise,
the second antenna 80b is connected to second network 82 by an
access point 70b. The digital signal from spectrometer 20 is
transmitted by transmitter 30 to first network 81 and is then
transmitted to the directional antenna 80a by being relayed over
the nodes of first network 81. The digital signal can then be
transmitted to second directional antenna 80b on second network 82.
Second network 82 then relays the digital signal to processing
device 32, display device 33 and/or the storage device 34.
FIG. 12 shows the communication between spectrometer 20 and
processing unit 32 via an existing wireless network 39. The data
from spectrometer 20 is fed into a transmitter 30 located in or
attached to spectrometer 20. Transmitter 30 can be, for example,
the type of transmission device used in a conventional cell phone.
Transmitter 30 then connects to the processing device 32 equipped
with a receiver 31 (e.g., a receiver used in current cell phone
technology) by opening a communication channel specific to the
processing device 32 on wireless network 39 (e.g., dialing a cell
phone number). Once the communication channel is established, the
digital signal is then transferred to processing device 32 by
routing the digital signal through the existing wireless network
39. Processing device 32 can then be connected to another network
or a display device and/or storage device. Wireless network 39 can
be any suitable network, such as, for example, SkyTel or Nokia's
communication network. In certain embodiments, wireless network 39
can be included as part of a wireless LAN, wireless WAN,
cellular/PCS network (e.g., by using a transceiver equipped with a
CPDP modem), digital phone network, proprietary packet switched
data network, One-way Pager, a Two-way Pager, satellite, Wireless
local loop, Local Multi-point Distribution Service, Personal Area
Network, and/or free space optical networks.
FIG. 13 shows the communication between the spectrometer 20 and an
application server 60 via a wireless network. Spectrometer 20 sends
the digital signal to transmitter 30, which can be, for example,
Xircon's Redhawk II.TM.. Transmitter 30 then wirelessly sends the
digital signal to processing device 32, which can be, for example,
a laptop computer, and to a long range transmission device 61,
which transmits the digital signal to a base transceiver station 62
via a modulated radio wave. Then, through a T1 line 63, the digital
signal is transmitted to a base station controller 64, which in
turn transmits the digital signal to a mobile switching center 65.
Based on a pre-defined user setting, mobile switching center 65
transmits the digital signal to either an interworking function
device 66 or a short message center 67. If the digital signal is
sent to interworking function device 66, interworking function
device 66 then transmits the digital signal to an application
server 60. However, if the digital signal is sent to short message
center 67, short message center 67 routes the digital signal over
the Internet 68 and on to the application server 60. Application
server 60 provides for display of the digital signal, transfer of
the digital signal to a client of server 60, analysis of the
digital signal, and/or storage of the digital signal. Application
server 60 can be any suitable device, such as, for example, an IBM
compatible Gateway PC.
It should be apparent that the FIGS. 1 13 show merely exemplary
embodiments, and other embodiments will be apparent to one skilled
in the art.
FIGS. 14A B show an illustrative remote spectrometer for performing
spectral scans. As illustrated in FIG. 14A, a multiple wavelength
photometer has light source 21 that produces a light beam that is
focused and directed onto granulation 6 by focusing optics 25. The
light that is transmitted through granulation 6 is passed through a
linear variable filter 120 to an array detector 121 in order to
filter and receive a number of specific, predetermined narrow bands
of wavelengths simultaneously. Linear variable filters are well
known in the art and are described in, for example, U.S. Pat. No.
6,057,925 to Anthon, U.S. Pat. No. 5,166,755 to Gat and U.S. Pat.
No. 5,218,473 to Seddon et al., and are shown schematically in FIG.
14B. Focusing optics 25 can form a portion of wall 11 of hopper 10.
In other embodiments, focusing optics 25 can be located outside
hopper 10, in which case the light beam passes through window 16 in
hopper 10 after impinging on focusing optics 25. Likewise, linear
variable filter 120 and array detector 121 may form a portion of
wall 11 of hopper 10. In other embodiments, linear variable filter
120 and array detector 121 can be located outside hopper 10, in
which case the light beam passes through a second window in hopper
10 and then impinges on linear variable filter 120. Most
preferably, linear variable filter 120 and array detector 121 may
be used and positioned very much in the same way as focusing optics
25 and detector 26 are used and positioned in the embodiments and
versions discussed elsewhere herein, such as those shown in FIGS.
1A 1F and FIGS. 2 3 and 6.
FIGS. 15A and 15B illustrate spectroscopic detector arrangements.
As shown in FIG. 15A, the device includes a light emitting portion
214 and two detectors 215, 216 that surround light emitting portion
214 and can be embedded in the wall of hopper 10. Light emitting
portion 214 has a light source that could be any light source, such
as a quartz halogen lamp with integrated focusing optics or a fiber
optic bundle, and light emitting portion 214 preferably has a
rectangular prism SiO.sub.2 light guide. At predetermined
intervals, light emitting portion 214 emits light onto granulation
6. Detectors 215,216 then detect the light reflected off
granulation 6. Detectors 215,216 are preferably formed of silicon
and are preferably designed to detect only a specific range of
wavelengths. For example, detector 215 could be set to detect light
at wavelengths of only 400 700 nm, and detector 216 could be set to
detect light at wavelengths of only 600 1100 nm. As such, the
device shown in FIG. 15A would be able to detect light wavelengths
of 400 1100 nm.
In one embodiment, detectors 215,216 can detect light at their
specific wavelength ranges due to the presence above each filter
215,216 of an optical filter that restricts the transmission of
light to detectors 215,216 at wavelengths in only the respective
specified ranges.
In another embodiment, detectors 215,216 are array detectors and
can detect light at their specific wavelength ranges due to the
presence above each detector 215,216 of a linear variable filter
120, as shown in FIGS. 14A B, that restricts the transmission of
light to detectors 215,216 at wavelengths in only the specified,
predetermined narrow band of wavelengths.
In a further preferred embodiment of a remote spectrometer, as
shown in FIG. 15B, the device includes a light emitting portion 214
and three detectors 217,218,219 that surround light emitting
portion 214. Light emitting portion 214 has a light source that
could be any light source but is preferably a quartz halogen lamp
with integrated focusing optics, and light emitting portion 214
preferably has a triangular prism SiO.sub.2 light guide. At
predetermined intervals light emitting portion 214 emits light onto
granulation 6. Detectors 217-219 then detect the light reflected
off granulation 6. The spectrometer of FIG. 15B is similar to the
spectrometer of FIG. 15A, except that light emitting portion 214 is
located among three detectors, rather than two detectors in FIG.
15A.
Detectors 217 219 are designed to detect only specific bands of
wavelengths. For example, detectors 217 219 are preferably formed
of silicon, with detector 217 detecting light at wavelengths of 400
700 nm, and detector 218 detecting light at wavelengths of 600 1100
nm. In addition, detector 219 is preferably formed of
indium/gallium/arsenic (InGaAs) and detects light at wavelengths of
11 1900 nm. As such, the device can detect light wavelengths of 400
1900 nm. In one embodiment, detectors 217 219 can detect light at
their specific wavelength ranges due to the presence above each
detector 217 219 of an optical filter that restricts the
transmission of light to detectors 217 219 at wavelengths in only
the specified ranges. In another embodiment, detectors 217 219 are
array detectors and can detect light at their specific wavelength
ranges due to the presence above each detector 217 219 of a linear
variable filter 120, as shown in FIGS. 14A B, that restricts the
transmission of light to detectors 217 219 at wavelengths in only
the specified, predetermined narrow band of wavelengths.
Most preferably, the embodiments of FIGS. 15A B may be used and
positioned very much in the same way as filter 23 and detector 26
are used and positioned in the embodiments and versions discussed
elsewhere herein, such as those shown in FIGS. 1A 1F and FIGS. 2 3
and 6.
FIG. 16 illustrates the manner in which a remote wireless
spectrometer can interact with a central computer. The present
invention, which can be made in accordance with any of the possible
embodiments described above, is generally considered to be situated
at a pharmaceutical manufacturing plant. The spectrometer 20 is
connected, either directly or wirelessly, to a base module 151 that
could also be situated at the pharmaceutical manufacturing
plant.
In certain preferred embodiments, a further remote communication
link 152 is provided between home base computer 151 and a central
or main computer 153. This link 152 could be by wireless satellite
cable, LAN, telephone link or any other suitable wireless
connection, and could be directly from home base computer 151 to
main computer 153. Main computer 153 receives and stores the
spectral scan from the present invention. Main computer 153 may
also monitor the purity of the granulation, including moisture
changes in the granulation's profile as well as trends therein,
performs analysis thereof, generates and regenerates the a modeling
equation for each sample as necessary, generates reports, and
performs business transactions and other tasks.
FIG. 17 shows in more particular detail the elements of a base
connection to the main computer. Spectrometer 20 is connected,
either directly or wirelessly, such as via a RS-232 Blue Tooth.RTM.
(Wireless link, to a base module 151. The remote communication link
152 between home base computer 151 and main computer 153 can be
additionally by existing dedicated telephone line, such as by
dial-up modem, by wireless communication such as satellite cable,
LAN, by internet, such as by cable or DSL, or even through a
virtual private network (VPN) or any other suitable wireless
connection. Main computer 153 preferably comprises a file server
155 that is linked to a database 157 through a scheduler/sender
156. Database 157 is also linked to calculations 158, archive 159
and file reader 160 modules.
Referring again to FIG. 16, in certain circumstances, spectrometer
20 of the present invention can be detached from hopper 10 and
transported and attached to another hopper 10. Such a device could
obtain the spectrographic data from a variety of different
locations. Modeling equations and results can be stored in a
compact flash card 161 that is attached to spectrometer 20.
Spectrometer 20 can be connected, either directly or wirelessly, to
a portable base module 162, such as a PALM.RTM. device 162a or a
laptop computer 162b, that typically comprises a processing unit
and a display device. Portable base module 162 could also be
wirelessly linked to home base computer 152 for downloading and
compilation of data. Portable base module 162 could also be
wirelessly linked 165 to main computer 153. As discussed
previously, these links 165 could be by wireless satellite cable,
LAN, telephone link or any other suitable wireless connection.
FIGS. 18A B show a preferred embodiment of a remote spectrometer
20. As illustrated in FIG. 18A, light source 21 produces a light
beam that is passed through granulation 6, through linear variable
filter 320, through slit aperture 322 and onto single diode
detector 321. As in the embodiments described above with reference
to FIGS. 1A F, the light from light source 21 may pass through near
infrared or infrared window/transparent element 25. For example,
spectrometer 20 can be set within the window 16 in the hopper 10
wall. After being transmitted through granulation 6 (as shown in
FIG. 18E), or reflected off of granulation 6 (as shown in FIG.
18F), the light is passed through linear variable filter 320
(possibly via a detector imaging optic), in order in order to
filter the light to a desired band of wavelengths. The light is
then detected by single diode detector 321, either as transmittance
or reflectance. In one embodiment, linear variable filter 320 can
be arranged as a single range filter, and detector 321 is a single
range detector.
The embodiment shown in FIGS. 18A B is a scanning module because
the device is equipped with piezoelectric bimorph (bender) 302 for
moving linear variable filter 320 in various directions in order to
allow the operator to obtain filtered scans of granulation 6 at a
number of specific, predetermined narrow band of wavelengths in the
light. Bimorph 302, powered by power supply 300, is connected to
linear variable filter 320 via fulcrum 304 and lever 306, which
amplify the displacement of the bimorph. FIG. 18A shows bimorph 302
with power supply 300 off. FIG. 18B shows bimorph 302 with power
supply 300 on. With power supply 300 on, bimorph 302 bends as shown
in FIG. 18B, forcing the lower portion of lever 306 to pivot about
fulcrum 304 in the direction of arrow A. The pivoting of lever 306
causes linear variable filter 320 to move in the direction of arrow
B, as indicated. To select each desired wavelength, power supply
300 may be controlled so as to provide predetermined power levels
to bimorph 302 and thereby translate linear variable filter 320 to
a desired position.
In another embodiment, linear variable filter 320 comprises
separate multi-range filters 223a,223b,223c, as shown in top view
in FIG. 18c. In this embodiment, each of linear variable filters
223a,223b,223c restricts the transmission of light to wavelengths
in only certain specified, predetermined narrow band of
wavelengths. For example, linear variable filter 223a transmits
light at wavelengths of 400 700 nm, linear variable filter 223b
transmits light at wavelengths of 600 1100 nm, and linear variable
filter 223c transmits light at wavelengths of 1100 1900 nm. The
separate multi-range linear variable filters 223a, 223b, 223c maybe
moved by respective piezoelectric bimorphs. When separate
multi-range filters 223a,223b,223c are used, separate detectors may
also be used to detect light at only those specific bands of
wavelengths. For example, as shown in top view in FIG. 1SD,
detector 321 is comprised of separate detectors 226a,226b,226c such
that detector 226a detects light at wavelengths of 400 700 nm,
detector 226b detects light at wavelengths of 600 1100 nm, and
detector 226c detects light at wavelengths of 1100 1900 nm. As
such, the device can detect light wavelengths of 400 1900 nm.
The operation of this device will be shown with regard to the
multi-range filter and detector embodiment but applies equally to
the single range filter and detector embodiment. The operator
programs the processing device (not shown) as to the desired
wavelengths or ranges of wavelengths to be scanned, and the
piezoelectric bimorphs move linear variable filters 223a,223b,223c
so as to allow only the desired wavelengths to pass. Thus, the
light 21 is filtered to the desired band of wavelengths by linear
variable filters 223a,223b,223c is focused onto array detectors
226a,226b,226c, through detector imaging optic 225 (or one for each
of detectors 226a,226b,226c), which detect light at the specific
wavelength ranges.
Alternatively, the operator may operate the device manually so as
to allow scans to be taken at only the particular wavelengths
specified at the time by the operator.
The embodiment of the invention shown in FIGS. 19A B is "solid
state" in the sense that no electric motor is used to move linear
variable filter 320. Piezoelectric bimorph 302 may be capable of
very precise and repeatable positioning to within fractions of a
micron, allowing for advantageous wavelength reproducibility.
Linear variable filter 320 may be, for example, 2 3 mm in length,
thereby enabling a relatively small overall size of spectrometer
20. Spectrometer 20 may be used in a wavelength range from
ultraviolet to the mid infrared (200 nm 10,000 nm) by selecting the
appropriate combination of linear variable filter 320 and single
diode detector 321.
Thus, an apparatus for analyzing for monitoring homogeneity and
detecting stratification of a granulation of pharmaceutical
components as they are being prepared in a dosage form has been
disclosed. One skilled in the art will appreciate that the present
invention can be carried out in other ways and practiced by other
than the described embodiments. The present embodiments therefore
should be considered in all respects as illustrative, and the
present invention is limited only by the claims that follow.
* * * * *